ACTIV-5 / Big Effect Trial (BET-A) for the Treatment of COVID-19

• ClinicalTrials.gov Identifier: NCT04583956
• Recruitment Status: Completed
• First Posted: October 12, 2020
• Results First Posted: December 19, 2022
• Last Update Posted: May 16, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.

The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.

One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.

The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

Condition or disease	Intervention/treatment	Phase
COVID-19	Other: Placebo; Drug: Remdesivir; Biological: Risankizumab	Phase 2

Detailed Description:

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.

The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.

One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.

The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.

The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8. The key secondary objectives are 1) to evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.

Contacts:

20-0013 Central Contact

Telephone: 1 (301) 7617948

Email: DMIDClinicalTrials@niaid.nih.gov

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 214 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
• Actual Study Start Date: October 23, 2020
• Actual Primary Completion Date: September 13, 2021
• Actual Study Completion Date: September 13, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Remdesivir + Placebo; 200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 1200-mg IV risankizumab placebo infusion (300-mg x 4 vials) once on Day 1. N=100.	Other: Placebo; Risankizumab placebo will be given at an equal volume at the same schedule.; Drug: Remdesivir; Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
Experimental: Remdesivir + Risankizumab; 200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 1200-mg IV risankizumab infusion (300-mg x 4 vials) once on Day 1. N=100.	Drug: Remdesivir; Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524.; Biological: Risankizumab; Risankizumab is a humanized immunoglobulin (Ig) G1 antagonistic monoclonal antibody (mAb) directed against the p19 subunit of the human cytokine interleukin-23. Risankizumab is formulated in a buffer of 4.4 mM disodium succinate hexahydrate/succinic acid, 225 mM sorbitol, 0.2 mg/mL polysorbate 20, and WFI in a 6R vial.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 [ Time Frame: Day 8 ]
   The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

Secondary Outcome Measures :

1. Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29 [ Time Frame: Day 1 through Day 29 ]
   Ordinal scale categories include 8) Death and 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO). Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Results are reported as Kaplan Meier estimates.
2. Time to Sustained Recovery [ Time Frame: Day 1 through Day 60 ]
   Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.
3. Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15 [ Time Frame: Day 15 ]
   The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
4. Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29 [ Time Frame: Day 29 ]
   The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
5. Change From Baseline in C-Reactive Protein (CRP) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
   Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
6. Change From Baseline in Ferritin [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
   Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
7. Change From Baseline in D-dimer [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
   Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
8. Change From Baseline in Fibrinogen [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
   Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
9. Change From Baseline in Alanine Aminotransferase (ALT) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
   Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
10. Change From Baseline in Aspartate Transaminase (AST) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
11. Change From Baseline in Hemoglobin [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
12. Change From Baseline in Creatinine [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
13. Change From Baseline in International Normalized Ratio (INR) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
14. Change From Baseline in Platelets [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
15. Change From Baseline in Bilirubin [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
16. Change From Baseline in White Blood Cell (WBC) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
17. Change From Baseline in Neutrophils [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
18. Change From Baseline in Eosinophils [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
19. Change From Baseline in Basophils [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
20. Change From Baseline in Lymphocytes [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
21. Change From Baseline in Monocytes [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
22. Number of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) [ Time Frame: Day 1 through Day 60 ]
    Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
23. Number of Participants Reporting Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 60 ]
    An SAE is defined as an AE or suspected adverse reaction that is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
24. Number of Participants Who Discontinued or Temporarily Suspended Study Treatment [ Time Frame: Day 1 through Day 29 ]
    Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration.
25. Duration of Hospitalization [ Time Frame: Day 1 through Day 29 ]
    Duration of hospitalization is defined first as the total number of days hospitalized for COVID-19, including readmissions for COVID-19-related reasons. It is also calculated as the total number of days hospitalized, including any readmissions for any reason.
26. Days of New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    Duration of new invasive mechanical ventilation/ECMO use was measured in days among participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died.
27. Days of Non-invasive Ventilation/High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    Duration of non-invasive ventilation or high flow oxygen use was measured in days among participants who required non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
28. Days of New Non-invasive Ventilation/High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants not on non-invasive ventilation/high flow oxygen at baseline who progressed to non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
29. Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use is defined as participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died during the study.
30. Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    New Non-invasive Ventilation/High Flow Oxygen Use is defined as participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline who progressed to non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study.
31. Mean Change in Ordinal Scale [ Time Frame: Day 1, 3, 5, 11, 15, 22, 29 ]
    The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities;2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4)Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement.
32. Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 [ Time Frame: Day 29 ]
    Ordinal scale categories include 8) Death and 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO). Defined as the proportion of participants who were alive and were not hospitalized on invasive mechanical ventilation or ECMO at the Day 29 visit.
33. 14-day Participant Mortality [ Time Frame: Day 1 through Day 15 ]
    The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.
34. 28-day Participant Mortality [ Time Frame: Day 1 through Day 29 ]
    The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.
35. 59-day Participant Mortality [ Time Frame: Day 1 through Day 60 ]
    The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates.
36. Days of Supplemental Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    Duration of supplemental oxygen use was measured in days among participants who required any supplemental oxygen, non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
37. Time to an Improvement of One Category From Baseline Using an Ordinal Scale [ Time Frame: Day 1 through Day 60 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
38. Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale [ Time Frame: Day 1 through Day 60 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
39. Time to Death [ Time Frame: Day 1 through Day 29 ]
    The time death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.
40. Days of Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adult >/= 18 years of age at time of enrollment.
5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test [NAAT], antigen test) in any respiratory specimen or saliva </=14 days prior to randomization.
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or ECMO (ordinal score 5, 6, or 7).

7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception from the time of screening through 5 months post study IP dosing.

   Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.

8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.

Exclusion Criteria:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal.

2. Subjects with a low glomerular filtration rate (eGFR), specifically:

   1. Subjects with an a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation.
   2. All subjects with an a glomerular filtration rate (eGFR) <20 mL/min (including hemodialysis and hemofiltration) are excluded.
3. Pregnancy or breast feeding.
4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
5. Allergy to any study medication.
6. Received five or more doses of remdesivir prior to screening.
7. Received two or more doses of > 60 mg of prednisone or equivalent in the 7 days prior to screening.
8. Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
9. Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 [e.g., anakinra, canakinumab], anti-IL-6 [e.g., tocilizumab, sarilumab, sitlukimab]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
10. Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
11. Received Granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
12. Received other immunosuppressants in the 4 weeks prior to screening and in the judgment of the investigator, the risk of immunosuppression with risankizumab is larger than the risk of Coronavirus Disease 2019 (COVID-19).
13. Received any live vaccine in the 4 weeks prior to screening.
14. Known active tuberculosis.
15. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
16. History of pulmonary alveolar proteinosis (PAP).
17. Has a malignancy and currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
18. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
19. Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
20. Previous participation in an ACTIV-5/Big Effect Trial (BET)

Contacts and Locations

Locations

United States, Arizona

The University of Arizona - Banner University Medical Center Tucson Campus - Tucson

Tucson, Arizona, United States, 85724-0001

United States, California

Kern Medical Center

Bakersfield, California, United States, 93306-4018

Hoag Hospital Newport Beach

Newport Beach, California, United States, 92663

Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases

Stanford, California, United States, 94305-2200

United States, Colorado

Penrose Hospital - Emergency Medicine

Colorado Springs, Colorado, United States, 80907

St. Francis Medical Center

Colorado Springs, Colorado, United States, 80923

St. Anthony Hospital

Lakewood, Colorado, United States, 80228-1704

St. Anthony Hospital North Health Campus

Westminster, Colorado, United States, 80023

United States, Connecticut

Nuvance Health Danbury Hospital - Infectious Disease

Danbury, Connecticut, United States, 06810

Yale School of Medicine - The Anlyan Center for Medical Research & Education - Immunobiology

New Haven, Connecticut, United States, 06519-1612

Nuvance Health - Norwalk Hospital - Asthma Pulmonary and Critical Care Medicine

Norwalk, Connecticut, United States, 06856

United States, Georgia

Grady Memorial Hospital

Atlanta, Georgia, United States, 30303

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, United States, 30030-1705

United States, Illinois

Cook County Health and Hospitals System - Ruth M Rothstein CORE Center

Chicago, Illinois, United States, 60612

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Massachusetts

Brigham and Women's Hospital - Infectious Diseases

Boston, Massachusetts, United States, 02115-6110

Boston Medical Center - Center for Infectious Diseases - Shapiro Center

Boston, Massachusetts, United States, 02118-2526

United States, Minnesota

Hennepin Healthcare Research Institute

Minneapolis, Minnesota, United States, 55415

United States, Nebraska

University of Nebraska Medical Center- Infectious Diseases

Omaha, Nebraska, United States, 68105

United States, New Jersey

Englewood Hospital

Englewood, New Jersey, United States, 07631

United States, New York

Jacobi Medical Center

Bronx, New York, United States, 10461-1119

The State University of New York - University at Buffalo - Department of Medicine

Buffalo, New York, United States, 14203

Mount Sinai School of Medicine - Medicine - Infectious Diseases

New York, New York, United States, 10029-6504

Nuvance Health - Vassar Brothers Medical Center

Poughkeepsie, New York, United States, 12601

United States, North Carolina

Wake Forest Baptist Health - Infectious Diseases

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

University of Toledo Medical Center - Ruppert Clinic

Toledo, Ohio, United States, 43614

United States, Pennsylvania

Doylestown Hospital

Doylestown, Pennsylvania, United States, 18901

United States, Rhode Island

Kent County Memorial Hospital

Warwick, Rhode Island, United States, 02886

United States, South Dakota

Monument Health - Clinical Research

Rapid City, South Dakota, United States, 57701

United States, Texas

Hendrick Health - Hendrick Medical Center

Abilene, Texas, United States, 79601

Baptist Hospitals of Southeast Texas Site

Beaumont, Texas, United States, 77701

United States, West Virginia

West Virginia University - Infectious Diseases Clinic

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study Protocol  [PDF] September 21, 2021

Statistical Analysis Plan  [PDF] May 23, 2022

Informed Consent Form  [PDF] February 11, 2021

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT04583956
• Other Study ID Numbers: 20-0013A
• First Posted: October 12, 2020
• Results First Posted: December 19, 2022
• Last Update Posted: May 16, 2023
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Adults; COVID-19; Multicenter; Platform; Putative; Therapeutics

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Remdesivir; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents